Skaggs Hollie S, Xing Hongyan, Wilkerson Donald C, Murphy Lynea A, Hong Yiling, Mayhew Christopher N, Sarge Kevin D
Department of Molecular and Cellular Biochemistry, Chandler Medical Center, University of Kentucky, 741 S. Limestone Street, Lexington, KY 40536-0084, USA.
J Biol Chem. 2007 Nov 23;282(47):33902-7. doi: 10.1074/jbc.M704054200. Epub 2007 Sep 25.
Stress conditions inhibit mRNA export, but mRNAs encoding heat shock proteins continue to be efficiently exported from the nucleus during stress. How HSP mRNAs bypass this stress-associated export inhibition was not known. Here, we show that HSF1, the transcription factor that binds HSP promoters after stress to induce their transcription, interacts with the nuclear pore-associating TPR protein in a stress-responsive manner. TPR is brought into proximity of the HSP70 promoter after stress and preferentially associates with mRNAs transcribed from this promoter. Disruption of the HSF1-TPR interaction inhibits the export of mRNAs expressed from the HSP70 promoter, both endogenous HSP70 mRNA and a luciferase reporter mRNA. These results suggest that HSP mRNA export escapes stress inhibition via HSF1-mediated recruitment of the nuclear pore-associating protein TPR to HSP genes, thereby functionally connecting the first and last nuclear steps of the gene expression pathway, transcription and mRNA export.
应激条件会抑制mRNA的输出，但编码热休克蛋白的mRNA在应激期间仍能继续有效地从细胞核输出。热休克蛋白mRNA如何绕过这种与应激相关的输出抑制尚不清楚。在此，我们表明，热休克因子1（HSF1），即应激后与热休克蛋白启动子结合以诱导其转录的转录因子，以应激反应方式与核孔相关的TPR蛋白相互作用。应激后，TPR靠近热休克蛋白70（HSP70）启动子，并优先与从该启动子转录的mRNA结合。HSF1-TPR相互作用的破坏会抑制从HSP70启动子表达的mRNA的输出，包括内源性HSP70 mRNA和荧光素酶报告基因mRNA。这些结果表明，热休克蛋白mRNA的输出通过HSF1介导的将核孔相关蛋白TPR募集到热休克蛋白基因上而逃避应激抑制，从而在功能上连接了基因表达途径的第一步和最后一步，即转录和mRNA输出。
